Cranial nerve cells (neurons) are main elements for controlling survival of higher order animals. Once the neurons are developed, they do not divide at all and only gradually exfoliate or go through necrosis. Exfoliation of the neurons occurs in the normal state but is particularly accelerated by genetic diseases, brain ischemia, or status epilepticus, or under conditions of poor nutrition and low oxygen. Some disorders of cranial nerves associated with aging (e.g., dementia) result from deficiency of an absolute amount of functional neurons caused by accumulation of exfoliated neurons. Thus, the monitoring and control of the exfoliation, as well as regeneration of the functions of neurons, are the most demanding subject to be solved among the aging problems.
Cranial nerve cells do not divide at all after the differentiation in the process of development, and maintain their functions or is accompanied by gradual deterioration of their functions throughout the life-time of the individual. They are presumed to have specific division-interrupting and function-maintaining mechanisms although these mechanisms have not yet been clarified. In the central nervous system, there exist numbers of unknown proteins and signaling substances, particularly stimulating substances and receptors thereof involved in brain-specific signal transduction, but many of their material basis still remains unknown.
Much research has been conducted worldwide on such an important element that controls the survival and maintenance of the cranial nerve cells. However, only a few elements were clarified in the substance or molecule level, and, prior to everything, it was necessary to develop techniques for discovery and analysis of those novel elements. Recently, the group of Dr. Masashi Yanagisawa and his colleagues of the University of Texas, Medical Research Center (authorized by the Howard Hughes Foundation) has succeeded in developing a technique for randomly screening neuropeptides and receptors thereof by using cultured cell and they have found a substance (named orexin) that directly binds to and stimulates the aperitive center in the hypothalamnus, and identified functions of the substance's receptor (Cell, 92, 573-585, 1998). However, such a systematic screening of substances is rare, and currently, stimulating factors involved in brain-specific signal transduction and receptors thereof are not yet fully clarified.
Under such circumstances, the present inventor and colleagues constructed an improved expressed complementary DNA (cDNA) library, developed a systematic screening technique, and succeeded in extraction and selection of genes specific for cranial nerve cells and found Bradeion α and β, whose expression occurs in brain, heart, and specific cancers only (U.S. application Ser. No. 09/440,936 filed Nov. 16, 1999). Bradeion β is also disclosed as a human cell division regulator in U.S. Pat. No. 5,871,973 and No. 5,928,899.
The object of this invention is to clarify the correlation between the presence of Bradeion α or β and specific cancers, and to utilize it for treatment of the cancers.